Intraocular pressure is maintained by a balance between rates of formation and outflow of aqueous humor. Adrenergic drug effects on aqueous formation is paradoxical in that both beta agonists and beta antagonists decrease formation and are effective ocular hypotensives in glaucoma therapy. The cellular site(s) that responds to adrenergic drugs in the iris/ciliary body probably involves adenylate cyclase. The same cellular sites regulating aqueous formation in the vascular and ciliary epithelial cells also constitute the blood/aqueous barrier. The barrier is damaged by inflammatory release of endogenous substances (prostaglandins, thromboxanes and prostacyclins) but also by specific agents such as alpha melanocyte stimulating hormone and possibly by cholera toxin. These agents have profound effects on adenylate cyclase and their actions in iris and ciliary body, like those of adenergic drugs may be mediated through adenylate cyclase. This proposal is a comprehensive study of the regulatory effects of adrenergic drugs and other agents such as alpha-MSH and cholera toxin on adenylate cyclase enzymes of iris and ciliary tissue. A careful analysis of adenylate cyclase regulation by receptor ligands will be obtained by quantitative dose-response data for agonists and antagonists with beta 1 and beta 2 specificity, and for the recently proposed alpha 1 and alpha 2 subclasses of adreno receptors. The dose response data will be generated from receptor ligand sensitive activations of membrane bound adenylate cyclase mediated via the guanyl nucleotide regulatory site of the cyclase enzyme. Cholera-toxin treated preparations, which have enhanced receptor sensitivity in presence of GTP, and the imido analog of GTP (GppNHp) will be used. Antagonists will be characterized in terms of their pA2 values for blockade of agonist-induced cyclase activation obtained by Schild plots of the dose-response data. The aim of this study is to identify, on the basis of their drug sensitivity, different adenylate cyclase-linked receptors involved in vascular regulation of blood flow, fluid transport and permeability across capillary endothelium, and fluid transport/secretion of ciliary epithelia in the iris and ciliary body.